Time-dependent alterations of vancomycin-induced nephrotoxicity in mice

Masaki Takigawa, Hirofumi Masutomi, Yuki Kishimoto, Yoshitomo Shimazaki, Yoshitomo Hamano, Yoshitaka Kondo, Tomio Arai, Jaewon Lee, Toshihiro Ishii, Yoshiko Mori, Akihito Ishigami*

*この研究の対応する著者

研究成果: Article査読

5 被引用数 (Scopus)

抄録

Vancomycin hydrochloride (VCM) is a glycopeptide antibiotic that is commonly used against methicil-lin-resistant, Gram-positive cocci despite the nephrotoxic side effects. VCM-induced nephrotoxicity has been reported in 5–28% of recipient patients. Therefore, renal failure induced by VCM has become an important clinical problem. However, the exceedingly complex mechanism of VCM-induced nephrotoxicity is not fully understood. Therefore, this study was designed to clarify time-dependent alterations of VCM-induced nephrotoxicity in mice as a step toward decreasing the risks of kidney injury associated with VCM therapy. VCM was injected intraperitoneally into mice at a dose of 400mg/kg body weight at 24-h intervals for 3, 5, 7, and 14d. At 24h after the last injection, we examined histopathological alterations of the kidney as well as blood biochemistry. VCM administration resulted in a decrease of body weight and increase of kidney weight. Histological examination revealed renal damage such as dilated proximal tubules with occasional casts and interstitial fibrosis in VCM-treated mice. Furthermore, immunohistochemical staining with anti-CD10 and anti-single-stranded DNA antibodies highlighted damaged renal proximal tubules with marked dilatation as well as numerous apoptotic cells as early as day 4 of VCM-treatment. The severity of symptoms progressed until day 15. These results suggest that VCM-induced renal damage and incipient renal failure begin soon after the start of treatment and progressively worsen. This is the first report describing the time-dependence of VCM-induced nephrotoxicity in mice and depicting a model that clarifies the mechanisms of this tissue damage.

本文言語English
ページ(範囲)975-983
ページ数9
ジャーナルBiological and Pharmaceutical Bulletin
40
7
DOI
出版ステータスPublished - 2017
外部発表はい

ASJC Scopus subject areas

  • 薬理学
  • 薬科学

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